CA2899170C - Compositions and methods of use in treating metabolic disorders - Google Patents
Compositions and methods of use in treating metabolic disorders Download PDFInfo
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- CA2899170C CA2899170C CA2899170A CA2899170A CA2899170C CA 2899170 C CA2899170 C CA 2899170C CA 2899170 A CA2899170 A CA 2899170A CA 2899170 A CA2899170 A CA 2899170A CA 2899170 C CA2899170 C CA 2899170C
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/475—Growth factors; Growth regulators
- C07K14/495—Transforming growth factor [TGF]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/18—Growth factors; Growth regulators
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/18—Growth factors; Growth regulators
- A61K38/1841—Transforming growth factor [TGF]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/475—Growth factors; Growth regulators
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/76—Albumins
- C07K14/765—Serum albumin, e.g. HSA
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/31—Fusion polypeptide fusions, other than Fc, for prolonged plasma life, e.g. albumin
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Zoology (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Diabetes (AREA)
- Molecular Biology (AREA)
- Toxicology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Child & Adolescent Psychology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
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| US201361758456P | 2013-01-30 | 2013-01-30 | |
| US61/758,456 | 2013-01-30 | ||
| US201361882542P | 2013-09-25 | 2013-09-25 | |
| US61/882,542 | 2013-09-25 | ||
| PCT/US2014/013232 WO2014120619A2 (en) | 2013-01-30 | 2014-01-27 | Compositions and methods of use in treating metabolic disorders |
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| CA2899170A1 CA2899170A1 (en) | 2014-08-07 |
| CA2899170C true CA2899170C (en) | 2022-08-02 |
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| CA2899170A Active CA2899170C (en) | 2013-01-30 | 2014-01-27 | Compositions and methods of use in treating metabolic disorders |
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| US (4) | US9828415B2 (OSRAM) |
| EP (1) | EP2950807B1 (OSRAM) |
| JP (1) | JP6272907B2 (OSRAM) |
| KR (1) | KR101993714B1 (OSRAM) |
| AU (1) | AU2014212640B2 (OSRAM) |
| BR (1) | BR112015018104A2 (OSRAM) |
| CA (1) | CA2899170C (OSRAM) |
| RU (1) | RU2704285C2 (OSRAM) |
| WO (1) | WO2014120619A2 (OSRAM) |
Families Citing this family (54)
| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2010101628A2 (en) | 2009-03-02 | 2010-09-10 | Massachusetts Institute Of Technology | Methods and products for in vivo enzyme profiling |
| WO2012125808A1 (en) | 2011-03-15 | 2012-09-20 | Massachusetts Institute Of Technology | Multiplexed detection with isotope-coded reporters |
| CN104204218A (zh) | 2012-01-26 | 2014-12-10 | 安姆根有限公司 | 生长分化因子15 (gdf-15)多肽 |
| CA2862516C (en) | 2012-03-27 | 2023-02-14 | Ngm Biopharmaceuticals, Inc. | Compositions and methods of use for treating metabolic disorders |
| US9161966B2 (en) | 2013-01-30 | 2015-10-20 | Ngm Biopharmaceuticals, Inc. | GDF15 mutein polypeptides |
| JP6272907B2 (ja) | 2013-01-30 | 2018-01-31 | エヌジーエム バイオファーマシューティカルズ インコーポレイテッド | 代謝障害の処置における組成物及び使用方法 |
| CN105452481A (zh) | 2013-06-07 | 2016-03-30 | 麻省理工学院 | 基于亲和力检测配体编码的合成性生物标记物 |
| CN105980400B (zh) * | 2013-07-31 | 2021-05-07 | 美国安进公司 | 生长分化因子15(gdf-15)构建体 |
| US10588980B2 (en) | 2014-06-23 | 2020-03-17 | Novartis Ag | Fatty acids and their use in conjugation to biomolecules |
| US20170107248A1 (en) * | 2014-06-23 | 2017-04-20 | Novartis Ag | Site specific protein modifications |
| WO2015198199A1 (en) * | 2014-06-23 | 2015-12-30 | Novartis Ag | Hsa-gdf-15 fusion polypeptide and use thereof. |
| JP6696915B2 (ja) | 2014-06-24 | 2020-05-20 | ノヴォ ノルディスク アー／エス | Ｍｉｃ−１融合タンパク質及びその使用 |
| TWI710570B (zh) | 2014-07-30 | 2020-11-21 | 美商Ｎｇｍ生物製藥公司 | 用於治療代謝異常之組成物及方法 |
| WO2016069925A1 (en) | 2014-10-30 | 2016-05-06 | Acceleron Pharma Inc. | Methods and compositions using gdf15 polypeptides for increasing red blood cells |
| AP2017009828A0 (en) * | 2014-10-31 | 2017-03-31 | Ngm Biopharmaceuticals Inc | Compositions and methods of use for treating metabolic disorders |
| WO2016102580A1 (en) * | 2014-12-22 | 2016-06-30 | Novo Nordisk A/S | Alpha-1-antitrypsin (a1at) fusion proteins and uses thereof |
| WO2017024182A1 (en) | 2015-08-04 | 2017-02-09 | Duke University | Genetically encoded intrinsically disordered stealth polymers for delivery and methods of using same |
| US11752213B2 (en) | 2015-12-21 | 2023-09-12 | Duke University | Surfaces having reduced non-specific binding and antigenicity |
| WO2017109706A1 (en) | 2015-12-22 | 2017-06-29 | Novartis Ag | Methods of treating or ameliorating metabolic disorders using growth differentiation factor 15 (gdf-15) |
| WO2017121865A1 (en) | 2016-01-15 | 2017-07-20 | Novo Nordisk A/S | Mic-1 receptor and uses thereof |
| SG11201807279QA (en) | 2016-03-31 | 2018-09-27 | Ngm Biopharmaceuticals Inc | Binding proteins and methods of use thereof |
| EP3440013A4 (en) * | 2016-04-08 | 2021-03-17 | Massachusetts Institute of Technology | METHODS FOR SPECIFICALLY PROFILING PROTEASE ACTIVITY AT LYMPHATIC GANGLIONS |
| EP3452407B1 (en) | 2016-05-05 | 2024-04-03 | Massachusetts Institute Of Technology | Methods and uses for remotely triggered protease activity measurements |
| US10336812B2 (en) | 2016-05-10 | 2019-07-02 | Janssen Biotech, Inc. | GDF15 fusion proteins and uses thereof |
| KR102433503B1 (ko) | 2016-05-24 | 2022-08-18 | 노보 노르디스크 에이/에스 | Mic-1 화합물 및 이것의 사용 |
| US11467156B2 (en) | 2016-06-01 | 2022-10-11 | Duke University | Nonfouling biosensors |
| WO2018057847A1 (en) | 2016-09-23 | 2018-03-29 | Duke University | Unstructured non-repetitive polypeptides having lcst behavior |
| US11648200B2 (en) | 2017-01-12 | 2023-05-16 | Duke University | Genetically encoded lipid-polypeptide hybrid biomaterials that exhibit temperature triggered hierarchical self-assembly |
| CA3059358A1 (en) | 2017-04-07 | 2018-10-11 | Massachusetts Institute Of Technology | Methods to spatially profile protease activity in tissue and sections |
| WO2018213320A1 (en) | 2017-05-15 | 2018-11-22 | Duke University | Recombinant production of hybrid lipid-biopolymer materials that self-assemble and encapsulate agents |
| TWI710377B (zh) | 2017-05-23 | 2020-11-21 | 丹麥商諾佛 儂迪克股份有限公司 | Ｍｉｃ－１化合物及其用途 |
| WO2019006374A1 (en) | 2017-06-30 | 2019-01-03 | Duke University | ORDER AND DISORDER AS A DESIGN PRINCIPLE FOR STIMULI-SENSITIVE BIOPOLYMER NETWORKS |
| JP2020533302A (ja) | 2017-09-10 | 2020-11-19 | ノヴォ ノルディスク アー／エス | 肥満の治療において使用するためのｍｉｃ−１およびｇｌｐ−１ |
| WO2019147954A1 (en) | 2018-01-26 | 2019-08-01 | Duke University | Albumin binding peptide-drug (aibiped) conjugates and methods of making and using same |
| WO2019173332A1 (en) | 2018-03-05 | 2019-09-12 | Massachusetts Institute Of Technology | Inhalable nanosensors with volatile reporters and uses thereof |
| TWI724392B (zh) | 2018-04-06 | 2021-04-11 | 美商美國禮來大藥廠 | 生長分化因子15促效劑化合物及其使用方法 |
| MX2020010659A (es) * | 2018-04-09 | 2020-10-28 | Amgen Inc | Proteinas de fusion del factor de diferenciacion de crecimiento 15. |
| WO2019213150A1 (en) | 2018-04-30 | 2019-11-07 | Duke University | Stimuli-responsive peg-like polymer-based drug delivery platform |
| US11649275B2 (en) | 2018-08-02 | 2023-05-16 | Duke University | Dual agonist fusion proteins |
| AU2019317813A1 (en) | 2018-08-10 | 2021-02-11 | Novartis Ag | GFRAL extracellular domains and methods of use |
| US12173349B2 (en) | 2018-09-25 | 2024-12-24 | Massachusetts Institute Of Technology | Lung protease nanosensors and uses thereof |
| MY205905A (en) | 2018-10-22 | 2024-11-20 | Janssen Pharmaceutica Nv | Glucagon like peptide 1 (glp1)-growth differentiation factor 15 (gdf15) fusion proteins and uses thereof |
| WO2020150560A1 (en) | 2019-01-17 | 2020-07-23 | Massachusetts Institute Of Technology | Sensors for detecting and imaging of cancer metastasis |
| EP3920955A4 (en) * | 2019-02-05 | 2023-02-22 | The Trustees of the University of Pennsylvania | GDNF FAMILY RECEPTOR-A-LIKE PEPTIDE LIGANDS (GFRAL) |
| WO2020185533A1 (en) * | 2019-03-08 | 2020-09-17 | Amgen Inc. | Growth differentiation factor 15 combination therapy |
| PE20220500A1 (es) * | 2019-04-23 | 2022-04-07 | Lg Chemical Ltd | POLIPEPTIDO DE FUSION QUE COMPRENDE LA REGION Fc DE INMUNOGLOBULINA Y GDF15 |
| US11512314B2 (en) | 2019-07-12 | 2022-11-29 | Duke University | Amphiphilic polynucleotides |
| US20230210950A1 (en) | 2019-10-04 | 2023-07-06 | Amgen Inc. | Use of gdf15 for treating cardiometabolic syndrome and other conditions |
| WO2021107603A2 (en) * | 2019-11-26 | 2021-06-03 | Yuhan Corporation | Long-acting gdf15 fusion protein and pharmaceutical composition comprising same |
| EP4087616A4 (en) * | 2020-03-04 | 2024-08-28 | Duke University | Protein nanoparticle design and application |
| EP4237438A4 (en) * | 2020-10-27 | 2024-11-27 | Beijing QL Biopharmaceutical Co., Ltd. | GDF15 FUSION PROTEINS AND THEIR USE |
| WO2022219495A1 (en) | 2021-04-12 | 2022-10-20 | Novartis Ag | 2-((4-((s)-2-(4-chloro-2-fluorophenyl)-2-methylbenzo[d][1,3]dioxol-4-yl)piperidin-1-yl)methyl)-1-(((s)-oxetan-2-yl)methyl)-1h-imidazole derivatives as activators of the glp1 receptor for the treatment of obesity |
| JP2025505198A (ja) | 2022-02-10 | 2025-02-21 | ノバルティス アーゲー | 肥満の治療のためのｇｌｐ１受容体の活性化因子としての２－（（４－（（ｓ）－２－（４－クロロ－２－フルオロフェニル）－２－メチルベンゾ［ｄ］［１，３］ジオキソール－４－イル）ピペリジン－１－イル）メチル）－１－（（（ｓ）－オキセタン－２－イル）メチル）－１ｈ－イミダゾール誘導体 |
| WO2023154953A1 (en) | 2022-02-14 | 2023-08-17 | Ngm Biopharmaceuticals, Inc. | Gdf15 polypeptides for treating and preventing autoimmune diseases |
Family Cites Families (92)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5194596A (en) | 1989-07-27 | 1993-03-16 | California Biotechnology Inc. | Production of vascular endothelial cell growth factor |
| FR2650598B1 (fr) | 1989-08-03 | 1994-06-03 | Rhone Poulenc Sante | Derives de l'albumine a fonction therapeutique |
| US5350836A (en) | 1989-10-12 | 1994-09-27 | Ohio University | Growth hormone antagonists |
| FR2686899B1 (fr) | 1992-01-31 | 1995-09-01 | Rhone Poulenc Rorer Sa | Nouveaux polypeptides biologiquement actifs, leur preparation et compositions pharmaceutiques les contenant. |
| WO1994003599A1 (fr) | 1992-08-04 | 1994-02-17 | Sagami Chemical Research Center | ADNc HUMAIN ET PROTEINE POUR LAQUELLE CODE CET ADNc |
| US6180602B1 (en) | 1992-08-04 | 2001-01-30 | Sagami Chemical Research Center | Human novel cDNA, TGF-beta superfamily protein encoded thereby and the use of immunosuppressive agent |
| JPH07250688A (ja) | 1994-01-28 | 1995-10-03 | Sagami Chem Res Center | ＴＧＦ−βスーパーファミリー蛋白質をコードするヒト新規ｃＤＮＡ |
| JPH07258293A (ja) * | 1994-03-23 | 1995-10-09 | Asahi Chem Ind Co Ltd | 新規な蛋白質ならびにその製造方法 |
| US5994102A (en) | 1994-12-15 | 1999-11-30 | Human Genome Sciences, Inc. | Polynucleotides encoding prostatic growth factor and process for producing prostatic growth factor polypeptides |
| US6521227B1 (en) | 1999-11-18 | 2003-02-18 | Peter L. Hudson | Polynucleotides encoding prostatic growth factor and process for producing prostatic growth factor polypeptides |
| AU1830195A (en) | 1994-12-15 | 1996-07-03 | Human Genome Sciences, Inc. | Prostatic growth factor |
| CA2225377C (en) | 1995-06-22 | 2013-08-13 | St. Vincent's Hospital Sydney Limited | Novel tgf-.beta. like cytokine |
| US6524802B1 (en) | 1996-03-29 | 2003-02-25 | The Johns Hopkins University School Of Medicine | Methods of detecting growth differentiation factor-14 |
| JP2001500732A (ja) * | 1996-09-11 | 2001-01-23 | オーソ―マクニール・フアーマシユーチカル・インコーポレーテツド | 前立腺がんを治療するためのＴＮＦ―β様タンパク質、ならびに関連する核酸分子、医薬組成物および方法 |
| AU8591198A (en) | 1997-07-31 | 1999-02-22 | Johns Hopkins University School Of Medicine, The | Growth differentiation factor-15 |
| EP1100822A1 (en) | 1998-07-23 | 2001-05-23 | Smithkline Beecham Corporation | Secreted cysteine rich protein-6 (scrp-6) |
| US6465181B2 (en) | 1999-03-25 | 2002-10-15 | Abbott Laboratories | Reagents and methods useful for detecting diseases of the prostate |
| US6974684B2 (en) | 2001-08-08 | 2005-12-13 | Curagen Corporation | Therapeutic polypeptides, nucleic acids encoding same, and methods of use |
| CA2372119A1 (en) | 1999-05-17 | 2000-11-23 | Biopharm Gesellschaft Zur Biotechnologischen Entwicklung Und Zum Vertrie B Von Pharmaka Mbh | Neuroprotective properties of gdf-15, a novel member of the tgf-.beta. superfamily |
| AU2001261024A1 (en) | 2000-04-12 | 2001-10-30 | Delta Biotechnology Limited | Albumin fusion proteins |
| ATE384265T1 (de) | 2000-04-20 | 2008-02-15 | St Vincents Hosp Sydney | Diagnostischer assay mit dem makrophagen- inhibitorischen-zytokin-1 (mic-1) |
| AU2001288770A1 (en) | 2000-09-08 | 2002-03-22 | The Government Of The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services | A non-steroidal anti-inflammatory drug activated gene with anti-tumorigenic properties |
| CA2433439A1 (en) | 2000-12-29 | 2002-08-15 | Curagen Corporation | Proteins and nucleic acids encoding same |
| TW200526779A (en) | 2001-02-08 | 2005-08-16 | Wyeth Corp | Modified and stabilized GDF propeptides and uses thereof |
| WO2002072608A2 (en) | 2001-03-09 | 2002-09-19 | University Of Chicago | POLYMERIC IMMUNOGLOBULIN FUSION PROTEINS THAT TARGET LOW-AFFINITY FCηRECEPTORS |
| ATE549354T1 (de) | 2001-05-11 | 2012-03-15 | Amgen Inc | Peptide und damit zusammenhängende an tall-1 bindende moleküle |
| US20030053431A1 (en) | 2001-09-10 | 2003-03-20 | Lila Madour | Method for performing handoff in a radio telecommunications network |
| US20060253913A1 (en) | 2001-12-21 | 2006-11-09 | Yue-Jin Huang | Production of hSA-linked butyrylcholinesterases in transgenic mammals |
| EP2277910A1 (en) | 2001-12-21 | 2011-01-26 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| US7919084B2 (en) | 2002-06-17 | 2011-04-05 | St. Vincent's Hospital Sydney Limited | Methods of diagnosis, prognosis and treatment of cardiovascular disease |
| CA2390820A1 (en) | 2002-06-17 | 2003-12-17 | St. Vincent's Hospital Sydney Limited | Methods of diagnosis, prognosis and treatment of cardiovascular disease |
| CN1241946C (zh) | 2002-07-01 | 2006-02-15 | 美国福源集团 | 对多种细胞具刺激增生作用的人血清白蛋白重组融合蛋白 |
| US20040253207A1 (en) | 2002-11-08 | 2004-12-16 | Barnes-Jewish Hospital | Methods and compositions for prostate epithelial cell differentiation |
| US7348004B2 (en) | 2003-05-06 | 2008-03-25 | Syntonix Pharmaceuticals, Inc. | Immunoglobulin chimeric monomer-dimer hybrids |
| PL2441466T3 (pl) | 2004-04-13 | 2015-01-30 | St Vincents Hospital Sydney Ltd | Środek hamujący MIC-1 |
| US20090042780A1 (en) | 2004-05-20 | 2009-02-12 | Acceleron Pharma Inc | Modified TGF-Beta Superfamily Polypeptides and Related Methods |
| US7670595B2 (en) | 2004-06-28 | 2010-03-02 | Merck Patent Gmbh | Fc-interferon-beta fusion proteins |
| JP5372380B2 (ja) | 2005-01-24 | 2013-12-18 | ペプスキャン システムズ ベー．フェー． | 結合化合物、免疫原性化合物およびペプチド模倣体 |
| JP2007258293A (ja) | 2006-03-22 | 2007-10-04 | Fuji Electric Holdings Co Ltd | はんだ濡れ性評価装置およびはんだ濡れ性評価方法 |
| LT2004683T (lt) | 2006-03-24 | 2016-10-10 | Biogen Hemophilia Inc. | Pc5, kaip faktoriaus ix pro-peptidą apdorojantis fermentas |
| US8974748B2 (en) | 2007-04-05 | 2015-03-10 | Corning Incorporated | Dual inlet microchannel device and method for using same |
| BRPI0712496A2 (pt) | 2006-06-02 | 2012-09-25 | Wyeth Corp | peptìdeo isolado, composição compreendendo o referido peptìdeo, ácido nucléico isolado e métodos de purificar uma proteìna na superfamìlia do fator beta de transformação do crescimento (tgf-?) e de estabilizar uma solução contendo uma proteìna na superfamìlia tgf-b. |
| US7754689B2 (en) | 2006-06-02 | 2010-07-13 | Wyeth Llc | Finger-1 peptide analogs of the TGF-β superfamily |
| NZ574423A (en) * | 2006-07-26 | 2012-04-27 | Pepscan Systems Bv | Immunogenic compounds and protein mimics |
| BRPI0715126B8 (pt) | 2006-08-04 | 2021-07-27 | Medizinische Hochschule Hannover | métodos para avaliação do risco de intervenções cardíacas e usos à base de gdf-15 |
| WO2008133536A2 (en) | 2007-04-25 | 2008-11-06 | Akademia Medyczna Im. Piastow Slaskich We Wroclawiu | New stem cell lines, their application and culture methods |
| BRPI0814465B1 (pt) | 2007-07-26 | 2021-11-23 | Novagen Holding Corporation | Proteína de fusão, dímero, método para produzir uma proteína de fusão, linhagem de célula, usos de uma proteína de fusão e de uma composição farmacêutica e composição farmacêutica |
| CA2694863A1 (en) | 2007-08-16 | 2009-02-19 | Garvan Institute Of Medical Research | Agents and methods for modulating macrophage inhibitory cytokine (mic-1) activity |
| JP2011502106A (ja) | 2007-10-09 | 2011-01-20 | セントビンセンツ ホスピタル シドニー リミテッド | マクロファージ阻害性サイトカイン−１を除去又は不活性化して悪液質を治療する方法 |
| ES2543985T3 (es) | 2007-10-22 | 2015-08-26 | St Vincent's Hospital Sydney Limited | Métodos de pronóstico |
| AU2009204501B2 (en) | 2008-01-07 | 2015-02-12 | Amgen Inc. | Method for making antibody Fc-heterodimeric molecules using electrostatic steering effects |
| WO2009087190A1 (en) | 2008-01-08 | 2009-07-16 | Roche Diagnostics Gmbh | Means and methods for assessing the risk of patients presenting to emergency units based on gdf-15 |
| EP2242505A4 (en) | 2008-01-08 | 2012-03-07 | Biogenerix Ag | GLYCOCONJUGATION OF POLYPEPTIDES USING OLIGOSACCHARYLTRANSFERASES |
| JP2011523051A (ja) | 2008-05-20 | 2011-08-04 | エフ．ホフマン−ラ ロシュ アーゲー | １型糖尿病におけるバイオマーカーとしてのｇｄｆ−１５ |
| WO2010007041A1 (en) | 2008-07-14 | 2010-01-21 | Roche Diagnostics Gmbh | Multimarker panel for diagnosing, monitoring and selecting the therapy for patients with heart failure |
| WO2010019263A2 (en) | 2008-08-15 | 2010-02-18 | Genzyme Corporation | Soluble flt constructs for treating cancers |
| CN102203619B (zh) | 2008-10-31 | 2015-12-16 | 圣文森特医院悉尼有限公司 | 慢性肾病中的预测方法 |
| KR102025158B1 (ko) | 2008-10-31 | 2019-09-25 | 얀센 바이오테크 인코포레이티드 | 인간 배아 줄기 세포의 췌장 내분비 계통으로의 분화 |
| EP2209003A1 (en) | 2009-01-16 | 2010-07-21 | F. Hoffmann-Roche AG | Means and methods for differentiating between fibrosis and cirrhosis |
| EP2211182A1 (en) | 2009-01-16 | 2010-07-28 | Roche Diagnostics GmbH | Method for the assessment of severity of liver cirrhosis |
| SG2014010680A (en) | 2009-02-12 | 2014-04-28 | Stryker Corp | Peripheral administration of proteins including tgf-beta superfamily members for treatment of systemic disorders and disease |
| GB0902737D0 (en) | 2009-02-19 | 2009-04-01 | Univ Gent | GDF15 as a differential marker for spondyloarthropathy |
| CA2752647A1 (en) | 2009-02-24 | 2010-09-02 | The Salk Institute For Biological Studies | Designer ligands of tgf-beta superfamily |
| UY38740A (es) * | 2009-05-05 | 2020-12-31 | Amgen Inc | Mutantes de fgf21 y usos del mismo |
| EP2451840B1 (en) | 2009-07-08 | 2018-12-26 | Amgen Inc. | Design of stable and aggregation free antibody fc molecules through ch3 domain interface engineering |
| WO2011008956A2 (en) | 2009-07-15 | 2011-01-20 | Zirus, Inc. | Mammalian genes involved in infection |
| WO2011050407A1 (en) | 2009-10-28 | 2011-05-05 | St Vincent's Hospital Sydney Limited | Methods of diagnosing and prognosing colonic polyps |
| CA2780143A1 (en) | 2009-11-05 | 2011-05-12 | Genentech, Inc. | Methods and composition for secretion of heterologous polypeptides |
| WO2011064758A2 (en) | 2009-11-30 | 2011-06-03 | Pfizer Limited | Fusion protein |
| US9212221B2 (en) | 2010-03-03 | 2015-12-15 | Detroit R & D, Inc. | Form-specific antibodies for NAG-1 (MIC-1, GDF-15), H6D and other TGF-β subfamily and heart disease and cancer diagnoses |
| JP5791335B2 (ja) | 2010-04-07 | 2015-10-07 | 花王株式会社 | オルガノポリシロキサン化合物の製造方法 |
| US20130202564A1 (en) | 2010-04-09 | 2013-08-08 | University Of Southern California | Systems and Methods of Cell Activated, Controlled Release Delivery of Growth Factors for Tissue Repair and Regeneration |
| EP2383571A1 (en) | 2010-05-02 | 2011-11-02 | Prof. Hess Medical Consulting GmbH | Growth differntioation factor 15 (GDF 15) for risk prediction of diabetic foot ulcer |
| EP2796874B1 (en) | 2010-08-26 | 2017-03-08 | Roche Diagnostics GmbH | Use of biomarkers in monitoring a medication in a subject suffering from heart failure |
| EP2439535A1 (en) | 2010-10-07 | 2012-04-11 | F. Hoffmann-La Roche AG | Diagnosis of diabetes related heart disease and GDF-15 and Troponin as predictors for the development of type 2 diabetes mellitus |
| CN103533951B (zh) | 2011-04-08 | 2017-04-19 | 安姆根有限公司 | 使用生长分化因子15(gdf‑15)治疗或改善代谢障碍的方法 |
| US9469676B2 (en) | 2011-04-13 | 2016-10-18 | Bristol-Myers Squibb Company | Fc fusion proteins comprising novel linkers or arrangements |
| AR086823A1 (es) | 2011-06-30 | 2014-01-22 | Genentech Inc | Formulaciones de anticuerpo anti-c-met, metodos |
| CN109517059B (zh) | 2011-06-30 | 2023-03-28 | 中外制药株式会社 | 异源二聚化多肽 |
| CN104204218A (zh) * | 2012-01-26 | 2014-12-10 | 安姆根有限公司 | 生长分化因子15 (gdf-15)多肽 |
| CA2862516C (en) | 2012-03-27 | 2023-02-14 | Ngm Biopharmaceuticals, Inc. | Compositions and methods of use for treating metabolic disorders |
| WO2013192388A1 (en) | 2012-06-20 | 2013-12-27 | University Of Virginia Patent Foundation | Compositions and methods for regulating glucose homeostasis and insulin action |
| WO2014000042A1 (en) | 2012-06-27 | 2014-01-03 | Prince Henry's Institute Of Medical Research | COMPOSITIONS AND METHODS FOR MODIFYING TGF-β FAMILY LIGANDS |
| SG11201408526SA (en) | 2012-08-08 | 2015-03-30 | Roche Glycart Ag | Interleukin-10 fusion proteins and uses thereof |
| EP3689370A1 (en) | 2012-12-21 | 2020-08-05 | Aveo Pharmaceuticals Inc. | Anti-gdf15 antibodies |
| JP6272907B2 (ja) | 2013-01-30 | 2018-01-31 | エヌジーエム バイオファーマシューティカルズ インコーポレイテッド | 代謝障害の処置における組成物及び使用方法 |
| US9161966B2 (en) | 2013-01-30 | 2015-10-20 | Ngm Biopharmaceuticals, Inc. | GDF15 mutein polypeptides |
| RS57393B1 (sr) | 2013-03-15 | 2018-09-28 | Hoffmann La Roche | Il-22 polipeptiidi i il-22 fuzioni proteini i metode za njihovu upotrebu |
| CN105980400B (zh) | 2013-07-31 | 2021-05-07 | 美国安进公司 | 生长分化因子15(gdf-15)构建体 |
| US20160193295A1 (en) | 2013-07-31 | 2016-07-07 | Amgen Inc. | Stabilization of fc-containing polypeptides |
| TWI710570B (zh) | 2014-07-30 | 2020-11-21 | 美商Ｎｇｍ生物製藥公司 | 用於治療代謝異常之組成物及方法 |
| AP2017009828A0 (en) | 2014-10-31 | 2017-03-31 | Ngm Biopharmaceuticals Inc | Compositions and methods of use for treating metabolic disorders |
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2014
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- 2014-01-27 KR KR1020157023041A patent/KR101993714B1/ko not_active Expired - Fee Related
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| Publication number | Publication date |
|---|---|
| KR20150114512A (ko) | 2015-10-12 |
| EP2950807B1 (en) | 2018-03-28 |
| EP2950807A2 (en) | 2015-12-09 |
| JP6272907B2 (ja) | 2018-01-31 |
| AU2014212640A1 (en) | 2015-08-13 |
| US10323075B2 (en) | 2019-06-18 |
| AU2014212640B2 (en) | 2017-10-19 |
| RU2015136440A3 (OSRAM) | 2018-12-25 |
| US20200087366A1 (en) | 2020-03-19 |
| US20160200787A1 (en) | 2016-07-14 |
| RU2015136440A (ru) | 2018-12-25 |
| US20210388047A1 (en) | 2021-12-16 |
| EP2950807A4 (en) | 2016-11-02 |
| BR112015018104A2 (pt) | 2017-11-21 |
| US20180100003A1 (en) | 2018-04-12 |
| RU2704285C2 (ru) | 2019-10-25 |
| KR101993714B1 (ko) | 2019-06-28 |
| CA2899170A1 (en) | 2014-08-07 |
| HK1211497A1 (en) | 2016-05-27 |
| WO2014120619A2 (en) | 2014-08-07 |
| US9828415B2 (en) | 2017-11-28 |
| JP2016511752A (ja) | 2016-04-21 |
| WO2014120619A3 (en) | 2014-09-25 |
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